Were There Recent Waves Of Brain Evolution In Humans?

John Hawks looks at a recent study of recent genetic mutations in humans linked to their surmised functions. 

In theory, if human evolution make some key breakthroughs at times associated archaeologically with inferred timing of the appearance of new genes dealing with relevant functions to those developments, we could tell a story of genetic mutations leading to the dramatic success of our species. But, due to methodological issues and the weakness of the evidence, he comes down solidly in the agnostic camp at this point about this kind of narrative.

Did Archaic Hominins Use Fire?

A new study suggests that Homo naledi, an archaic hominin probably not directly ancestral to modern humans or Neanderthals or Denisovans, with remains found in a South African cave, used fire, according to an account from the Washington Post.

We were already pretty sure that Neanderthals also used fire, so it isn't a distinctly modern human innovation. But Neanderthals are fairly close to modern humans (so much so that non-African humans generally have Neanderthal admixture in their genomes) and had larger brains than modern human do, while Homo naledi is one of our more remote archaic hominin relatives and was smaller brained than modern humans.

Key Genetic Differences Between Humans And Other Hominins

We are starting to reach the point where comparisons of modern human DNA and ancient DNA can tell us fairly precisely how we differed from archaic hominins and which differences mattered the most. The New York Times explains the latest development on this front:

Scientists have discovered a glitch in our DNA that may have helped set the minds of our ancestors apart from those of Neanderthals and other extinct relatives.

The mutation, which arose in the past few hundred thousand years, spurs the development of more neurons in the part of the brain that we use for our most complex forms of thought, according to a new study published in Science on Thursday.

“What we found is one gene that certainly contributes to making us human,” said Wieland Huttner, a neuroscientist at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, and one of the authors of the study.

The most obvious feature of the human brain is its size — four times as large as that of chimpanzees, our closest living relatives.

Our brain also has distinctive anatomical features. The region of the cortex just behind our eyes, known as the frontal lobe, is essential for some of our most complex thoughts. According to a study from 2018, the human frontal lobe has far more neurons than the same region in chimpanzees does.

But comparing humans with living apes has a serious shortcoming: Our most recent common ancestor with chimpanzees lived roughly seven million years ago. To fill in what happened since then, scientists have had to resort to fossils of our more recent ancestors, known as hominins.

Inspecting hominin skulls, paleoanthropologists have found that the brains of our ancestors dramatically increased in size starting about two million years ago. They reached the size of living humans by about 600,000 years ago. Neanderthals, among our closest extinct hominin relatives, had brains as big as ours. . . .

But Neanderthal brains were elongated, whereas humans have a more spherical shape. Scientists can’t say what accounts for those differences. One possibility is that various regions of our ancestors’ brains changed size. . . .

In recent years, neuroscientists have begun investigating ancient brains with a new source of information: bits of DNA preserved inside hominin fossils. Geneticists have reconstructed entire genomes of Neanderthals as well as their eastern cousins, the Denisovans.

Scientists have zeroed in on potentially crucial differences between our genome and the genomes of Neanderthals and Denisovans. Human DNA contains about 19,000 genes. The proteins encoded by those genes are mostly identical to those of Neanderthals and Denisovans. But researchers have found 96 human-specific mutations that changed the structure of a protein.

In 2017, Anneline Pinson, a researcher in Dr. Huttner’s lab, was looking over that list of mutations and noticed one that altered a gene called TKTL1. Scientists have known that TKTL1 becomes active in the developing human cortex, especially in the frontal lobe. 

. . .

For their final experiment, the researchers set out to create a miniature Neanderthal-like brain. They started with a human embryonic stem cell, editing its TKTL1 gene so that it no longer had the human mutation. It instead carried the mutation found in our relatives, including Neanderthals, chimpanzees and other mammals.

They then put the stem cell in a bath of chemicals that coaxed it to turn into a clump of developing brain tissue, called a brain organoid. It generated progenitor brain cells, which then produced a miniature cortex made of layers of neurons.

The Neanderthal-like brain organoid made fewer neurons than did organoids with the human version of TKTL1. That suggests that when the TKTL1 gene mutated, our ancestors could produce extra neurons in the frontal lobe. While this change did not increase the overall size of our brain, it might have reorganized its wiring.

As a post-script, it is hard to understate the incredibly advanced the work is to extract ancient DNA samples, and to make sense of the DNA.

What Drives The Distribution Of Tonal Languages And Correlated Phonetic Features?

This post was originally started and mostly written a few years ago. It is refined, expanded, and published now. (I've now cleared my backlog of draft posts.)

Languages with Complex Tone Systems

Languages With Simple Tone Systems

Languages Without Tone Systems

Languages with labial-velar consonants in yellow; 

languages with clicks in red and black.

Languages with glottal consonants other than ejectives

Purple and yellow have implosives only; 

red and white have glottalized resonants only; 

green and aqua have implosives and glottalized resonants.

Charts via WALS Online.

What is a tonal language?

In a tonal language, tone is the term used to describe the use of pitch patterns to distinguish individual words or the grammatical forms of words, such as the singular and plural forms of nouns or different tenses of verbs.

Tonality appears to be a part of a total phoneme set for a language which also includes a language's inventory of consonants, glottal stops, vowels, and click sounds. 

Tonality tends to be associated with a larger number of other phonemes as well.

* The average language with a complex tone system has 26.0 consonants and 7.05 vowels, for a total of 33.05 phonemes.

* The average language with a simple tone system has 23.3 consonants and 6.28 vowels, for a total of 29.58 phonemes.

* The average language with no tone system has 22.1 consonants and 5.58 vowels, for a total of 27.68 phonemes.

Tonal languages also tend to be more likely to have implosive consonants (a type of glottal consonant), glottal resonant consonants, labial-velar consonants, and linguistic click consonants.

Where Are Tonal Languages Spoken?

As the charts at the top of this post demonstrate, tone languages tend to be more vastly common in places that with tropical (or at least subtropical) climates and very rare elsewhere. 

Languages with simple tone systems show a similar, but less pronounced tendency. All of the tonal languages outside tropical and subtropical areas have only simple tone systems. 

Some of the more controversial cases are arguable cases of simple tone systems in places where tonal languages are rare.  A dozen of the languages classified as having simple tone systems are among the most geographically atypical and are only marginally tonal to the extent that they arguably would be more properly classified as non-tonal. These include Norwegian, Japanese, Ainu and Oneida (Iroquoian; New York State).

Much of South Asia, however, despite having many languages, has a tropical or subtropical climate, but appears to have no languages with a complex tone system among its many Indo-European, Dravidian, or Austroasiatic languages, although it does have a handful of Sino-Tibetan languages with simple tone systems in the highlands found in the Himalayas and in the far northeast of the subcontinent. 

There are definitional issues about what constitutes a language with a complex tone system, a simple tone system or no tone system. WALS explains its definitions (emphasis added):

The first distinction made in this chapter is between languages with and languages without tones. For most languages it is easy to determine if the language does or does not make use of tone, but there are surprisingly sharp disagreements in certain cases. 

For example, Dar Fur Daju (Nilo-Saharan; Sudan) is reported as non-tonal in one source but transcribed with three tone levels in another. Ket (Yeniseian; northern Siberia) is described as having none, two, four or eight tones by different authors (there are some differences in the dialects being described, but this does not account for the differences of opinion on the tonal status of the language). Both these languages have been counted as non-tonal in the present chapter since the opinion that they lack tones seems to be the most well-supported (see Thelwall 1981 and Feev 1998 respectively).  

Other languages have clear word-level pitch phenomena but with limited function, or with roles that look more like stress in that they highlight a particular syllable of a word. Norwegian, Japanese, Ainu and Oneida (Iroquoian; New York State) are among languages of this kind. These languages are classified here as tonal, but are perhaps only marginally so.  

Of the 526 languages included in the data used for this chapter, 306 (58.2%) are classified as non-tonal. This probably underrepresents the proportion of the world’s languages which are tonal since the sample is not proportional to the density of languages in different areas. 

For example, from the large Niger-Congo family of Africa there are 68 languages in the sample, 5 of which are nontonal (Swahili, Diola-Fogny, Koromfe, Wolof and Bisa) and the remainder tonal. The Ethnologue (Grimes 2000) lists 1489 Niger-Congo languages, so less than 5% of the Niger-Congo languages are included. 

Of the Indo-European languages of western and central Europe, 16 are included (5 Romance, 3 Germanic, 3 Slavic, 2 Celtic, 1 Baltic, Greek, and Albanian). In these Indo-European groups the Ethnologue lists a total of 145 languages (7 Celtic, 58 Germanic, 48 Italic, 18 Slavic, 7 Greek, 4 Albanian, and 3 Baltic languages), so that over 10% of the Western European languages listed are included, only two of which are tonal or marginally so and the rest non-tonal. 

If, correspondingly, 10% of the Niger-Congo family had been included, 80 additional tone languages would have been included. 

Languages without tones predominate in the western part of the Eurasian landmass, including South Asia, in the more southerly regions of South America, and in the coastal area of northwestern North America. In this last area great genealogical diversity exists among the indigenous languages, but tone is almost entirely absent. In addition, no Australian language has been reported to be tonal.  

The languages with tones are divided into those with a simple tone system — essentially those with only a two-way basic contrast, usually between high and low levels — and those with a more complex set of contrasts. 

About a quarter of the languages (132, or 25.1%) have simple tone systems. This includes 12 languages which appear to meet the definition of being tonal only marginally. With better information a few of these might end up being classed as non-tonal. 

Less than a fifth (88, or 16.7%) have complex tone systems. Tone languages have marked regional distributions. Virtually all the languages in Africa are tonal, with the greater number having only simple tone systems, although more complex systems are not unusual, especially in West Africa. Languages with complex tone systems dominate in an area of East and Southeast Asia. Several clusters of languages with tones occur in South, Central and North America. A number of the languages of New Guinea are also tonal, or at least marginally so.

Tonality Appears To Be Primarily An Areal Rather Than A Language Family Based Property Of Languages

There are language families in which some languages are tonal, while other are not.

As noted above, two Indo-European languages arguably have simple tone systems, although at least one of these is a marginal case with a dubious classification.

Only five of Africa's Niger-Congo languages do not have tone systems.

Within the Afroasiatic language family, tonal languages appear in the Omotic, Chadic, and Cushitic branches of Afroasiatic (the Southern tier of Afroasiatic languages, mostly in Ethiopia and the African Sahel), according to Ehret (1996), but the Semitic, Berber, and Egyptian branches do not use tones phonemically.

Most Austroasiatic languages are tonal, but not the Munda languages of South Asia and not five of the lesser known Austroasiatic languages of Vietnam and Laos.

The Austronesian languages aren't uniform with regard to tonality either: "Unlike in the languages of Mainland Southeast Asia, tonal contrasts are extremely rare in Austronesian languages. Exceptional cases of tonal languages are Moklen and a few languages of the Chamic, South Halmahera–West New Guinea and New Caledonian subgroups."

The locations have temperatures and humidities that influence sound transmission through the air, and have terrain influences (e.g. tree density) that impact how far away you would need words you speak to carry best. So, one theory is that tone languages arise in places where the sound transmission qualities of the air and terrain favor them.

There have been suggestions in the literature that the local climate and ecology can make certain phoneme sets better in some places than in others, that the nature of one part of a phoneme set influences the nature of other parts of the phoneme set, and that there are specific non-random factors that favor particular subtypes of phonemes in particular conditions.

An environmental explanation is supported by the observation that tonality in language seems to be more of an areal effect than one that tracks language families.  There is a fair amount of circumstantial evidence, when you look at patterns of semantic tone use globally in all sorts of languages, to suggest that tonality is more of an areal feature than it is an indicator of the ancestral source of a language. Neighboring languages that come from different families often share the feature of semantic tonality, while languages within the same language family often differ in their use of semantic tonality.

Incidentally, the geographic distribution of languages with tone systems is similar, although not identical, to the geographic distribution of languages with glottal consonants. Both are most common in sub-Saharan Africa, Southeast Asia, and the subtropical and tropical regions of the Americas (although the Americas are far from uniform despite all except the Na-Dene and Inuit language families probably having a common ancestor ca. 14kya). But, the Chinese dialect family uses tone, while it does not utilize glottal consonants. 

It could be that the ancestral hominin type ASPM gene correlated with tonal languages “tunes” ones hearing system to better distinguish sounds in a certain pitch range, in general, in places that that the temperatures, humidities and terrain most conducive to tonal languages, while the derived type ASPM gene loosens to focus of the hearing system so that it isn’t so primed to maximizing hearing of sounds in particular set of conditions, which would be adaptive elsewhere.

This is a more complex hypothesis than the one proposed in the paper showing a relationship between tonal languages and this gene. This 2007 paper and abstract are as follows:

The correlations between interpopulation genetic and linguistic diversities are mostly noncausal (spurious), being due to historical processes and geographical factors that shape them in similar ways. Studies of such correlations usually consider allele frequencies and linguistic groupings (dialects, languages, linguistic families or phyla), sometimes controlling for geographic, topographic, or ecological factors. 

Here, we consider the relation between allele frequencies and linguistic typological features. Specifically, we focus on the derived haplogroups of the brain growth and development-related genes ASPM and Microcephalin, which show signs of natural selection and a marked geographic structure, and on linguistic tone, the use of voice pitch to convey lexical or grammatical distinctions. 

We hypothesize that there is a relationship between the population frequency of these two alleles and the presence of linguistic tone and test this hypothesis relative to a large database (983 alleles and 26 linguistic features in 49 populations), showing that it is not due to the usual explanatory factors represented by geography and history. The relationship between genetic and linguistic diversity in this case may be causal: certain alleles can bias language acquisition or processing and thereby influence the trajectory of language change through iterated cultural transmission.

Dan Dediu and D. Robert Ladd, "Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin" 104 (26) PNAS 10944-10949 (June 26, 2007). https://doi.org/10.1073/pnas.0610848104

Earlier versions still of this gene are associated with brain size:

The size of human brain tripled over a period of approximately 2 million years (MY) that ended 0.2-0.4 MY ago. This evolutionary expansion is believed to be important to the emergence of human language and other high-order cognitive functions, yet its genetic basis remains unknown. An evolutionary analysis of genes controlling brain development may shed light on it. ASPM (abnormal spindle-like microcephaly associated) is one of such genes, as nonsense mutations lead to primary microcephaly, a human disease characterized by a 70% reduction in brain size. Here I provide evidence suggesting that human ASPM went through an episode of accelerated sequence evolution by positive Darwinian selection after the split of humans and chimpanzees but before the separation of modern non-Africans from Africans. Because positive selection acts on a gene only when the gene function is altered and the organismal fitness is increased, my results suggest that adaptive functional modifications occurred in human ASPM and that it may be a major genetic component underlying the evolution of the human brain.

The case that your ASPM variant enhances fitness primarily by making your hearing system better adapted to your primary environment makes more sense to me in an evolutionary selective fitness sense. If people with the region appropriate variant hear subtle slight sound differences better than people who lack it, that could increase the ability of a hunter-gatherer to locate prey, to detect predators, to locate lost children who have wandered far away, to hear your enemies coming to get you, to detect a fire that has gotten out of control or something that you are standing on that is about to break, and cumulatively, that could produce a gradual, put persistent selective fitness advantage in the evolutionary sense.

I find it harder to believe that the tone language specific application of this trait would have much of a selective fitness effect. An inability to distinguish by sound alone two words that would both make contextual sense in a tonal language that you and the speaker share might tweak one’s social status in the community a little, but it seems less likely to have a big impact on mortality or lifetime reproductive success. It’s not impossible, but it would seem like a weaker explanation.

Against this backdrop, the natural question to ask is one that wouldn’t otherwise be obvious, which is “why aren’t there more tonal language in South Asia?” which has substantial linguistic diversity and climate features in part of the region that are very similar to places in Africa, Southeast and East Asia, and the Americas where tonal languages are predominant.

One partial answer to this is that the Indo-Aryan languages developed in places that did not have this climate and didn’t spontaneously pick up this feature upon arriving in the subcontinent. 

Migration can also explain the affirmative presence of these features in arid southern Africa where people speaking these languages probably migrated from more tropical parts of Eastern sub-Saharan Africa.

But, this doesn’t explain why we don’t see tonal Munda and Dravidian languages in South Asia. The urheimat of the Austroasiatic languages of which the Munda languages are a family member, is Southeast Asia (or perhaps southern China), where the vast majority of languages are tonal. And, the Dravidian languages, as far as anyone knows, are autochthonous in South Asia.

In both of these exception cases, I think that the likely explanation is a language learner effect.

The Munda languages, at least initially, seem to have had a fairly northerly distribution within South Asia where hearing well suited to tonality wouldn’t have been advantageous to the local people who probably accounted for all or most of the women in the community at the time of first contact when the Munda languages would have been adopted by people integrated into the early Munda communities. If half the people had trouble hearing the tones, that feature which was almost surely present in an ancestral pre-Munda language probably didn’t survive.

In the case of the Dravidian languages, which probably have an ancestral version that was tonal under the environmental hypothesis, the pertinent fact is that there are no meaningful communities in Dravidian India that do not have substantial ANI admixture dating to the last 2000-3500 years. The language learner affect at the time of ANI-ASI admixture could have stripped the Dravidian languages in existence at the time of their tonal features for the same reasons. The ubiquity of the Hindu religion in Dravidian India which has clear Indo-Aryan and Harappan synthesis origins, likewise suggests that the language learners were not just anybody, they were culturally influential elites whose language choices tend to influence whole communities by cultural imitation.

Extinct Tasmanian Tiger's Brain Analyzed

This is like something out of a Steampunk novel or Jurassic Park. Cool!

The last known Tasmanian tiger (Thylacinus cynocephalus) - aka the thylacine - died in 1936. Because its natural behavior was never documented, we are left to infer aspects of its behavior from museum specimens and unreliable historical recollections. Recent advances in brain imaging have made it possible to scan postmortem specimens of a wide range of animals, even more than a decade old. Any thylacine brain, however, would be more than 100 years old. 

Here, we show that it is possible to reconstruct white matter tracts in two thylacine brains. For functional interpretation, we compare to the white matter reconstructions of the brains of two Tasmanian devils (Sarcophilus harrisii). We reconstructed the cortical projection zones of the basal ganglia and major thalamic nuclei. The basal ganglia reconstruction showed a more modularized pattern in the cortex of the thylacine, while the devil cortex was dominated by the putamen. Similarly, the thalamic projections had a more orderly topography in the thylacine than the devil. These results are consistent with theories of brain evolution suggesting that larger brains are more modularized. Functionally, the thylacine's brain may have had relatively more cortex devoted to planning and decision-making, which would be consistent with a predatory ecological niche versus the scavenging niche of the devil.

Gregory S. Berns, Ken W.S. Ashwell, "RECONSTRUCTION OF THE CORTICAL MAPS OF THE TASMANIAN TIGER AND COMPARISON TO THE TASMANIAN DEVIL" (October 26. 2016).
doi: http://dx.doi.org/10.1101/083592

A Quick Neuro-Linguistic Observation

The linguistic distinction between non-sex based gender systems or more than three genders for male, female and neuter (a common feature, for example, of Niger-Congo languages, Papuan languages, and Australian Aboriginal languages), and noun cases that are not called genders which are present in many other languages (which are numerous, for example in Caucasian and Dravidian languages), is a distinction without a difference in my opinion, that obscures possible relationships between languages based merely on regional and sub-disciplinary conventions about how grammatical features are named.

It is also notable that both these non-sex based gender systems and these noun case systems tend to correspond to taxonomies of nouns that neuroscientists have found of distinct modules of kinds of nouns in the human brain.  Thus, while these seem like arbitrary categories, these categories may be to a significant extent hardwired into our brains, which suggests that these categories were likely also part of many Upper Paleolithic human languages that were never attested.

The fact that these language features are most common in some of the language families derive from language families that have probably existed with very deep time depths also supports this hypothesis.

Key Gene Associated With Hominin Leap ID'd

What is it that makes humans different from other extant primates?

A new study points the finger at a small number of genes associated with brain development which are also have some connections to common developmental disorders and mental health conditions, and in particular to a gene called SRGAP2 which is one of the several dozen genes that seem to be most plausible candidates for genes that distinguish hominins from other great apes.

[L]oss of SRGAP2 function accelerates neurons' migration in the developing brain, potentially helping them reach their final destination more efficiently. Moreover, neurons that have decreased SRGAP2 function, due to expression of the human-specific SRGAP2 display more knob-like extensions or spines on their surfaces, making the neurons appear much more like those found in the human brain. These spines enable connections between neurons to form.

The authors of the study think the effect of this mutation would have been dramatic as soon as it emerged.  "If this gene duplication did indeed produce an immediate effect during evolution . . . there must have been a fascinating period in human history characterized by "huge variation" in human cognition and behavior." 

New Finding Hints At Common Mechanism in Alzheimer's And Autism

The amyloid precursor protein is typically the focus of research related to Alzheimer's disease. However, recent scientific reports have identified elevated levels of the particular protein fragment, called, sAPP-α, in the blood of autistic children. The fragment is a well-known growth factor for nerves, and studies imply that it plays a role in T-cell immune responses as well.

From here.

Abnormal immune function has been noted in children with autism before, but no cause had previously been identified. The new study suggests that this protein that is already a biomarker for Alzheimer's disease may also be a biomarker for autism. Alzheimer's disease is the most well known form of geriatric dementia, although pre-clinical signs of it may start to manifest as early as young adulthood.

Autism is typically first diagnosed in preschool children and narrow definition autism is a characteristic subtype of developmental disability found in 1 in 110 children that disproportionately affects boys that is part of an "Autism spectrum" that is found in more children and at the milder end is sometimes described as a form of mere neurodiversity.

The research suggest that it may be possible in a few years to do a blood test for autism, allowing for earlier diagnosis, which could be helpful if earlier treatments have a better chance of being effective, and could also reduce the risk of misdiagnosis leading to inappropriate treatment.

Brain Parasites That Affect Dopamine Found In 2/9th of Americans

[I]nfection by the brain parasite Toxoplasma gondii, found in 10-20 per cent of the UK's population, directly affects the production of dopamine, a key chemical messenger in the brain. . . . Toxoplasmosis, which is transmitted via cat faeces (found on unwashed vegetables) and raw or undercooked infected meat, is relatively common, with 10-20% of the UK population and 22% of the US population estimated to carry the parasite as cysts. Most people with the parasite are healthy, but for those who are immune-suppressed -- and particularly for pregnant women -- there are significant health risks that can occasionally be fatal.

The parasite infects the brain by forming a cyst within its cells and produces an enzyme called tyrosine hydroxylase, which is needed to make dopamine. Dopamine's role in mood, sociability, attention, motivation and sleep patterns are well documented and schizophrenia has long been associated with dopamine, which is the target of all current schizophrenia drugs on the market.

From here.

The role of dopamine in ADHD and schizophrenia is discussed here.

I certainly admit to being absolutely shocked to discover that there is any brain parasite in human beings that can impact an important brain subsystem with observable effects is anywhere near as common as Toxoplasma gondii. It brings to mind a subplot of some of Isaac Asimov's Foundation series in which a communicable disease affecting the brain is intentionally employed to prevent humanity from making certain kinds of scientific progress.

Usually the brain is unusually free of outside agents because the brain-blood barrier does a better job of keeping these agents out than the systems that protect the rest of the body. But, these cysts somehow manage to cross that barrier.

I would very much like to know if there are other common brain parasites out there, what percentage of carriers of this parasite suffer any symptoms from it, and what kind of diagnosis and treatment regimes are out there to deal with it. Even a quite low percentage of cases that are symptomatic could conceivably account for a quite high percentage of dopamine related conditions that do not have a clear genetic basis, and if I've never heard of it, the odds that it is not widely considered as a possibility by mental health professionals is substantial. This kind of causation suggests a very different treatment regime than the default assumption in mental health circles that a condition is congenital. More here (from 2007).

ADHD Genetic Inheritance Patterns

Attention deficit hyperactivity disorder (ADHD) appears to involve a large number of rare genetic variants rather than a few common causal genes, much as autism and schizophrenia do, and some of those rare genetic variants appear to overlap between ADHD and a fair number of other conditions. Autism is comordbid with ADHD about 75% of the time.

But, ADHD without a comorbid condition is predominantly familial in inheritance, rather than mostly arising from new mutations appearing for the first time in the person with that condition, reflecting its less genetic fitness impairing character.

Rare Gene Variants And Genetic Conditions

An important class of genetic conditions are caused by myriad rare genetic mutations that may emerge for the first time when the person who has it is born, or may be limited to small extended lineages or fairly small populations, rather than to all of humanity.

A small number of rare genetic mutations are produced in each new generation. Advanced parental age and environmental exposures and stresses can increase their frequency, the absence of these factors can reduce their frequency.

The most harmful of these rare genetic mutations are never passed on in the gene pool because they produce miscarriages or cognenital defects that cause someone to die before reproducing or to be infertile or both. Others appear where they are mostly harmless, for example in an inactivated gene or one triggered by environmental conditions that are absent (e.g. a gene that weakens ability to handle thin oxygen at high altitude in someone who lives on a flat Pacific island), and are passed on from generation to generation as little more than evolutionarily neutral ancestry informative markers.

Certain genes are more sensitive to disruption than others. The most sensitive genes code intricate biological processes that call upon many genes to work together to function properly which can be interrupted by defects in that biological system at a great many different points. Thus, interruptions to the same system at any of these different points is going to appear phenotypically as a similar syndrome associated with the overall complex biological system's failure to work properly due to some rare genetic variant.

Autism and schizophrenia are two of many conditions that seem to fit the profile of having overwhelmingly genetic causes that act on the same or interrelated groups of biological systems in a personn causing phenomenologically similar symptoms, but in which the specific mutations that cause the syndrome vary almost as widely as the number of extended families that have cases of it.

These genetic syndromes (as noted by my source linked above) adhere to "the “Anna Karenina principle”, based on Tolstoy’s famous opening line:
“Happy families are all alike; every unhappy family is unhappy in its own way”, people without these syndromes are are alike in the relevant genes (or least exhibit a handful of common variations in those genes); people with these syndromes all differ from this fixed standard in their own way.

These conditions can be among the most severely impairing of genetic conditions, because they rely for a substantial share of their prevalance on new mutations at each generation rather than Mendelin inheritance from parents. They don't have to be fitness enhancing to endure.

In contrast, genetic conditions whose prevalance relies on the precisely same mutation being passed on from parent to child need to either be genetic fitness neutral, or genetic fitness enhancing (at least at a long run multi-generational, extended familiy level of analysis), or the genetic fitness disadvantage nature of the mutation will cause its frequency in the population to decline unless other unrelated genetic fitness boosts cause the individual's population to expand notwithstanding its other faults.

The prevalance of these conditions is a product of mutation rates per generation and the proportion of the genome that constitutes a target area that would induce these conditions if a random mutation of some type arose there. The larger the group of genes required to code a biological function, the more vulnerable it is to this kind of condition. Given the extremely complexity of the brain relative to that of the brains of most other animals, and relative to many other parts of our bodies, it isn't too surprising that many of these rare gene variant disruptions of complex systems conditions give rise to mental health conditions.

Even if every known sufferer from autism and schizophrenia and everyone who was a potential carrier of those conditions was removed from a sufficiently control population, that control population would develop new autistic and schizophrenic individuals in the very next generation and would in not many generations after that have the same prevalance of autism and schizophrenia as the source populations if environmental factors that impact mutation rates were held constant between the source and control populations.

Spontaneous v. Familial Inheritance As A Matter of Degree

Of course, Mendelin inheritance models and sponanteous rare genetic variant models are merely ideal types. Every Mendelin inherited genetic variant started at some point as a spontaneously arising rare genetic mutation. Every rare genetic variant that is passed on to at least one child has a Mendelin inheritance element.

Rare genetic variants that are dominant in expression get noticed and classified by the conditions they give rise to, and have negative fitness effects, are going to have predominantly sporadic rather than familial prevalance patterns even though they are genetic.

Recessive rare genetic variants considered

Rare genetic variants that are recessive in expression are invisible until (1) inbreeding causes someone to have two copies of the recessive gene, probably many generations later, (2) someone who has already inherited a recessive gene from a parent spontaneously has a germline mutation in the same gene from another parent (either the same, or a functionally equivalent version), or (3) two independent lineages each have mutations in the same gene (possibly many generations apart from each other) in a manner that are recessive in effect and admixture of those lineages gives rise to an individual who expresses the recessive gene variant's effect.

Given the fairly modest number of mutations per generation (IIRC about 2500) out of 3 billion genetic bases in an individual's genome, method (1), or method (3) with different versions of the recessive mutation that have the same effect, are likely to be much more common than the alternatives and from the point of view of an individual born with a recessive genetic condition it is almost always going to look like a predominantly Mendelin inheritance based genetic condition.

The odds of one novel germ line mutation from a father and one novel germline mutation from a mother of the same recessive mutation in the same gene arising at the same time in the same individual is almost nil unless it is the product of intentional manipulation or a highly targeted environmental effect (e.g. lateral gene transfer as a result of a shared germ line retroviral infection, or an environmental effect that only impacts the very end point of a chromosome for chemical geometry reasons of some kind). There is some circumstantial evidence that a retrovirus carried by a seasonal germ vector like lice may account for the seasons variation in schizophrenia (and perhaps also autism) prevalence.

Also, recessive conditions, as a result, are likely to start somewhere and see their prevalance slowly grow in a particular reproductive population due to population expansion and founder effects, or due to major selective advantages associated with them, rather than having the more random, generally global prevalance one expects in syndroms caused by rare genetic variants that influence complex biological systems that have themselves reached fixation or near fixation on a species or population.

Tell Tale Symptoms Of New Mutation Rare Gene Variant Syndromes

Strongly hereditary conditions that show similar prevalance in all global populations, like schizophrenia, are more likely to be dominant genetic conditions caused to a great extent by new rare gene variant mutations in large complex biological systems, while strongly hereditary conditions that show major frequency variations between different populations are more likely to be associated with Mendelin recessive genes.

Rare gene variants that are fitness enhancing in almost all circumstances, in contrast, whether dominant additive, or recessive, such as new mutations that enhance intelligence, should have strongly familial inheritance patterns. Every time one of these arises, it should tend to stay in the genome and should tend to stall on the road to fixation only if it interfers with some other fitness enhancing gene (perhaps either gene individually changes brain chemistry in a positive way but the presence of both genes at the same time has no effect or a negative effect) or has other negative side effects (e.g. an enhancement of connective tissue development that fosters brain connectivity but also increases the risk at any given point in life of developing connective tissue cancer, a scenario that has been proposed as a hypothetical basis for the fairly rapid spread of one of the breast cancer risk genes).

Adventures In Chemicals The Affect The Brain And Seasonal Birth Effects

I've abstracted a hodgepodge of interesting new research studies on the impact of chemicals and birthdays on mental health.  We a finally reaching the frontier where the actual biological mechanism behind mental health conditions long believed to have a biological basis are understood in a meaningful fashion with clinical applications.

Cortisol hormone response patterns linked to temperament in toddlers

Cortisol responses to stress in toddlers reflect their temperaments and may also have significant environmental responses. Personality traits which otherwise seem to have only suggestive oppositions to each other seem to have a biological root as different dimensions of cortisol responses to stress. In particular, anxiety and depression may be the opposite side of the coin the same trait that at the other extreme may be associated with ADHD. It wouldn't overstate the matter to infer that the Big Five personality trait conscientiousness may also be linked to this tendency that is present in very early childhood.

Is your kid a "dove" -- cautious and submissive when confronting new environments, or perhaps you have a "hawk" -- bold and assertive in unfamiliar settings? . . .

Children exposed to high levels of interparental aggression at home showed different reactions to [a staged] telephone quarrel. Doves with parents who fought violently produced elevated levels of cortisol, a hormone that is thought to increase a person's sensitivity to stress. Hawks from such stressful home environments put the breaks on cortisol production, which is regarded as a marker for diminishing experiences of danger and alarm.

Heightened cortisol levels characteristic of the doves were related to lower attention problems but also put them at risk for developing anxiety and depression over time. By contrast, the lower cortisol levels for hawks in aggressive families were associated with lower anxiety problems; however, at the same time, these children were more prone to risky behavior, including attention and hyperactivity problems.

Previous research has focused more on neurotransmitters and general stimulants in these conditions.

Dopamine flows from anticipation of reward, not the reward itself.

The treatment of psychiatric conditions like depression or schizophrenia often revolves around regulating monoamine neurotransmitters like serotonin, norepinephrine and dopamine.

Dopamine is an important neurotransmitter that functions in a lot of behaviors and reactions, such as movement, lactation, aggression, fear, etc. In diseases like Parkinson, dopamine levels lower and movement becomes uncontrolled. In other diseases like schizophrenia, either dopamine levels are high or response to dopamine is higher, and paranoia & hallucinations manifest. Treating schizophrenia involves blocking dopamine receptors. As you can imagine, a common side effect of antipsychotics is movement disorders — or Parkinsonism. . . .

Our cultural and behavioral predisopostions ultimately boil down to chemicals in our brain interacting and stimulating other areas. One of the most important functions of dopamine is in the reward system of the brain, an area called the nucleus accumbens that primes pleasurable behavior to repeat, such as sex, eating, and drugs. . . .

Robert Sapolsky of Stanford Neurology makes the distinction between how dopamine levels rise in the anticipation of pleasure and not as a response to pleasure.

From here.

Drug Addition Linked To Salt Appetite System

[T]he gene patterns activated by stimulating an instinctive behavior, salt appetite, [a]re the same groups of genes regulated by cocaine or opiate (such as heroin) addiction.

"[B]locking addiction-related pathways . . . powerfully interfere[s] with sodium appetite. . . . [The] findings . . . could lead to a new understanding of addictions and the detrimental consequences when obesity-generating foods are overloaded with sodium. . . . Though instincts like salt appetite are basically genetic neural programs, they may be substantially changed by learning and cognition . . . Once the genetic program is operating, experiences that are part of the execution of the program become embodied in the overall patterns of an individual's behavior, and some scientists have theorized that drug addiction may use nerve pathways of instinct. . . . one classic instinct, the hunger for salt, is providing neural organization that subserves addiction to opiates and cocaine."

From here.

Ketamine Has Different Roles At Different Doses

Ketamine is finding new applications in both legal and illegal applications.

The anesthetic ketamine works against depression by quickly boosting levels of a brain compound that has been linked to the condition . . . [which] may lead to highly effective and fast-acting antidepressants that provide relief within hours instead of weeks. . . . Traditional antidepressants can be effective but often take weeks or months to improve symptoms. . . . “Here is increasing evidence that you can go more directly at the target, and that’s maybe why you get more of a rapid antidepressant effect.”

Mice receiving a single injection of ketamine showed fewer signs of depression just half an hour after the shot, and they continued to show multiple signs of reduced depression for a week. . . .

At high doses, ketamine renders a person unconscious. At lower doses, the drug can induce euphoria, hallucinations and out-of-body experiences, properties that make “Special K” a popular drug of abuse. . . . the study . . . used low doses that wouldn’t induce psychotic effects.

They found that ketamine kicks off a series of biochemical changes in the brain that culminate in the production of a protein called BDNF. Low BDNF levels have been linked to depression. . . . mice genetically engineered to be unable to produce BDNF didn’t respond to ketamine.

From here.

A small trial reported in 2010 found Ketamine to be safe and effective in treating treatment-resistant bipolar patients, suggesting that it acts on a different mechanism than existing depression treatments. Unlike traditional anti-depressants, whose efficacy has been seriously questioned as being little more than placebo effect in a significant class of patients treated with them, Ketamine's effect is so rapid and pronounced that its short term effectiveness is beyond question, although its tendency to be associated with mild psychiotic side effects is a concern.

British drug enforcement authorities have seen increased abuse of ketamine:

Once seen as a drug exclusively for the rave and dance scene, its popularity is now growing among Britain's middle-class users due to its price – a gram of ketamine costs £20, half as much as the same amount of cocaine – and the fact that it is seen as a "safe" and "clean" drug. . .

a survey carried out by Professor David Nutt, the chairman of the Government's drug advisory panel, ranks the class C drug as the sixth most dangerous illegal drug available – more harmful than Ecstasy and cannabis. The mistaken belief that the substance is risk-free is encouraging more young people to try ketamine and to take it in increasingly higher doses. . . . it can cause heart or lung failure and point to the fact that it has been linked to 23 deaths between 1993 and 2006. In 2006 it was classified as a class C drug [in the U.K.] . . . the drug, which can be snorted, swallowed, injected and even smoked, . . . [had] an estimated 60,000 users [in the U.K.] between 1998 and 2000 . . . [and] about 113,000 in 2008. . . .

Originally used to treat injured soldiers in Vietnam, ketamine is most commonly used now as a horse tranquilliser. It has also been experimented with to treat depression and alcohol and heroin addiction. It was classified as an illegal drug in 2006 by the UK Government. It is usually sold in powder or liquid form for about £20 per gram. Unlike cocaine and heroin, it is not physically addictive, but, like cannabis and Ecstasy, it is psychologically addictive.

David first tried ketamine as a 20-year-old student at university in London. Now a 27-year-old marketing executive, living in Shoreditch, east London, he still takes the drug once a month. "I see it as a fun, sociable drug," he said. "I do it at house parties or if I'm having a big night out. I used to do cocaine, but I suppose I gradually replaced coke with ket. Coke is much more expensive and it generally makes everyone very loud and aggressive. Ket is different. It costs less and you use it in smaller quantities so it lasts a lot longer. The feeling you get is different too. It makes you feel anaesthetised to your worries. You forget about your normal life and everything is euphoric. Sometimes I've had bad trips, but I've never felt angry when on ketamine. I think it is a lot safer too. I've read it can have long-term effects on your health, but it doesn't seem as dangerous as cocaine. When on coke I used to feel my heart pounding and it didn't feel right. The other reason I changed is because of the classification. I've got a proper job and a career and I don't want to lose that. Ketamine is a class C drug so if I get caught I'm probably only going to get a slap on the wrist."

Hallucinating Computers

Efforts to create neural network computer models of the brain's circuits for processing language in an effort to understand schizophrenic auditory hallucinations have managed to reproduce the phenomena of coherent auditory hallucinations (i.e. hearing voices) by both of two different mechanisms suspected to be a work in this phenomena in the real world.

Hearing voices is a hallmark of schizophrenia and other psychotic disorders, occurring in 60-80% of cases. These voices are typically identified as belonging to other people and may be voicing the person’s thoughts, commenting on their actions or ideas, arguing with each other or telling the person to do something. Importantly, these auditory hallucinations are as subjectively real as any external voices. They may in many cases be critical or abusive and are often highly distressing to the sufferer.

However, many perfectly healthy people also regularly hear voices – as many as 1 in 25 according to some studies, and in most cases these experiences are perfectly benign. In fact, we all hear voices “belonging to other people” when we dream – we can converse with these voices, waiting for their responses as if they were derived from external agents. Of course, these percepts are actually generated by the activity of our own brain, but how?

The two different models that were both supported in the computerized neural network were as follows:

There are two major hypotheses that were modelled: the first is that networks in schizophrenia are “over-pruned”. This fits with a lot of observations, including neuroimaging data showing reduced connectivity in the brains of people suffering with schizophrenia. It also fits with the age of onset of the florid expression of this disorder, which is usually in the late teens to early twenties. This corresponds to a period of brain maturation characterised by an intense burst of pruning of synapses – the connections between neurons.

In schizophrenia, the network may have fewer synapses to begin with, but not so few that it doesn’t work well. This may however make it vulnerable to this process of maturation, which may reduce its functionality below a critical threshold. Alternatively, the process of synaptic pruning may be overactive in schizophrenia, damaging a previously normal network. (The evidence favours earlier disruptions).

The second model involves differences in the level of dopamine signalling in these circuits. Dopamine is a neuromodulator – it alters how neurons respond to other signals – and is a key component of active perception. It plays a particular role in signalling whether inputs match top-down expectations derived from our learned experience of the world. There is a wealth of evidence implicating dopamine signalling abnormalities in schizophrenia, particularly in active psychosis. Whether these abnormalities are (i) the primary cause of the disease, (ii) a secondary mechanism causing specific symptoms (like psychosis), or (iii) the brain attempting to compensate for other changes is not clear.

Birth Season Effects On Mental Health

A causal mechanism isn't obvious, but some mental health conditions so seasonal effects.

Anorexia nervosa is more common among people born in the spring. . . . [Researchers] found an excess of anorexia births between March and June, and a deficit from September to October. . . . A number of previous studies have found that mental illnesses such as schizophrenia, bipolar disorder and major depression are more common among those born in the spring -- so this finding in anorexia is perhaps not surprising. . . .researchers believe that environmental factors around the time of conception or when the baby is developing in the womb may be responsible. . . . Seasonal changes in temperature, sunlight exposure and vitamin D levels, maternal nutrition and exposure to infections are all possible risk factors. Identifying these risk factors is important in helping us understand and maybe even prevent illness in future.

Meanwhile:

An examination of the birth records of the more than 7 million children born in the state of California during the 1990s and early 2000s has found a clear link between the month in which a child is conceived and the risk of that child later receiving a diagnosis of autism." The risk of having a child with an autism spectrum disorder grew progressively throughout the fall and winter to early spring, with children conceived in March having a 16 percent greater risk of later autism diagnoses, when compared with July conceptions.

The researchers said the finding suggests that environmental factors, for example, exposure to seasonal viruses like influenza, might play a role in the greater risk they found of children conceived during the winter having autism.

"The study finding was pronounced even after adjusting for factors such as maternal education, race /ethnicity, and the child's year of conception." . . . Each month was compared with July, with an 8 percent higher incidence in December, increasing to 16 percent higher in March.

The study lacked the means to discern if conception or some later point in pregnancy was the source of the vulnerability.